Verubecestat-MK-8931-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEVerubecestatCat.No.:HY-16759CASNo.:1286770-55-5Synonyms:MK-8931分⼦式:C₁₇H₁₇F₂N₅O₃S分⼦量:409.41作⽤靶点:Beta-secretase作⽤通路:NeuronalSignaling储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥35mg/mL(85.49mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.4425mL12.2127mL24.4254mL5mM0.4885mL2.4425mL4.8851mL10mM0.2443mL1.2213mL2.4425mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(6.11mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.11mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.11mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Verubecestat(MK-8931)⼀种具有⼝服活性的，⾼亲和⼒BACE1和BACE2抑制剂，Ki值分别为2.2nM和0.38nM。Verubecestat可以有效降低Aβ40，并具有⽤于阿尔茨海默⽒病的潜⼒。IC50&TargetKi:2.2nM(BACE1)and0.38nM(BACE2)[1]体外研究Verubecestat(MK-8931)isaβ-siteamyloidprecursorproteincleavingenzyme1/2(BACE1/2)inhibitor.VerubecestatdoesnotsignificantlyinhibithumanCYPisoforms1A2,2C9,2C19,2D6,and3A4(allIC50>40μM),indicatingthatthecompoundisunlikelytobeaperpetratorofCYP-mediateddrug-druginteractions[1].VerubecestathasIC50sof2.1nM,0.7nM,4.4nMforAβ1-40,Aβ1-42,sAPPβinHEK293APPSwe/Loncells[1].体内研究Verubecestat(MK-8931;3mg/kg;IVororal)hasaT1/2of1.9hours,aCLof46mL/min/kg,aVssof5.4L/kg,aCmaxof0.27μMandaAUCof1.1μM•hforSprague-Dawley(SD)rats[1].Verubecestat(1mg/kg;IV)hasaT1/2of4.9hours,aCLof21mL/min/kg,aVssof7.5L/kgforcynomolgusmonkeys[1].Verubecestat(1mg/kg;IV)hasaT1/2of9.7hours,aCLof4.3mL/min/kg,aVssof2.7L/kgforbeagledogs[1].Verubecestat(30mg/kg;orally;BIDfor5days)causesamodest(1.4-fold)inductionofCYP3A1activitybutdoesnotsignificantlyaltertheexpressionofCYPs1A1,1A2,2B,3A2,or4Ainrats[1].Verubecestatdose-dependentlyreducesCSFandcortexAβ40withED50valuesof5and8mg/kg,respectively,correspondingtounboundplasmaEC50valuesof48and81nM,respectively[1].Verubecestat(3and10mg/kg;orally)reducesprofound,sustainedofCSFAβ40levelsandhaspeakeffectsonCSFAβlowering(72and81%reductionat3and10mg/kg,respectively)12hafterdosing[1].AnimalModel:Sprague-Dawley(SD)rats[1]Dosage:3mg/kg(PharmacokineticAnalysis)Administration:IVororalResult:HadaT1/2of1.9hours,aCLof46mL/min/kg,aVssof5.4L/kg,aCmaxof0.27μMandaAUCof1.1μM•h.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE户使⽤本产品发表的科研⽂献•CellDeathDiffer.2022Jun22.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].YanR,etal.SteppingclosertotreatingAlzheimer'sdiseasepatientswithBACE1inhibitordrugs.TranslNeurodegener.2016Jul14;5:13.[2].ScottJD,etal.Discoveryofthe3-Imino-1,2,4-thiadiazinane1,1-DioxideDerivativeVerubecestat(MK-8931)-Aβ-SiteAmyloidPrecursorProteinCleavingEnzyme1InhibitorfortheTreatmentofAlzheimer'sDisease.MedChem.2016Dec8;59(23):10435-10450.McePdfHeightCaution:Product